Synthesis of N-Substituted 3-Aminomethylidenetetramic Acids

(S)-3-(Dimethylamino)methylidene-5-benzyltetramic acid derivatives 4a and 4b were prepared in three steps from N-protected (S)-3-phenylalanines la and 1b, respectively. Similarly, N-[N-(benzyloxycarbonyl)glycyl]glycine (1c) was transformed into the enaminone 4c. Acid-catalysed coupling of enaminones 4a-c with aliphatic, aromatic, and heteroaromatic primary amines 5-34 afforded the corresponding N(3')-substituted 3-aminomethylidenetetramic acid derivatives 35-64 in 29-96% yields.